Gene expression profiling may help in skin cancer management

Key takeaways:

• There are six gene expression profiling tools available or under investigation.
• Gene expression profiling may reduce the number of unnecessary biopsies.

Understanding the types of gene expression profiling available may help practitioners integrate these tools into their practices, according to a study.

“Current gene expression profiling (GEP) focuses on identifying and quantifying RNA transcripts in tissue samples,” Ryan Jay, DO, of the OhioHealth Riverside Community Hospital in Columbus, Ohio, and colleagues wrote. “Specific RNA transcripts and their expression levels reflect how the once living cells activated certain genes for eventual phenotypic expression.”

Using reverse transcriptase-polymerase chain reaction (RT-PCR) to revert specific RNA transcripts to DNA, GEP can uncover the tumor biology of various skin cancers.

In this study, the authors compiled a list of current GEPs that are available or under investigation for skin cancer.

23-GEP myPATH Melanoma

The purpose of 23-GEP myPATH Melanoma (Castle Biosciences) is to determine the risk of malignancy in suspected melanomas. With a sensitivity of 91.5% and a specificity of 92.5%, this test conducts quantitative RT-PCR to analyze the expression of 23 genes. Results are classified as either benign, intermediate or malignant.

35-GEP Diff-Dx-Melanoma

The 35-GEP Diff-Dx-Melanoma (Castle Biosciences) is similar to the 23-GEP myPATH Melanoma except this test analyzes the expression of 35 genes. With a slightly higher sensitivity (99.1%) and specificity (94.3%) compared with the 23-GEP, the test manufacturer recommends that the 35-GEP follow the 23-GEP when an intermediate risk is detected in the latter.

Pigmented Lesion Assay (PLA)

The Pigmented Lesion Assay (DermTech) patch aids in ruling out melanoma and reducing unnecessary surgical biopsies of benign lesions. The patch, which is placed on suspicious lesions, analyzes the adhered cells for PRAME and LINC00518 gene expression. A negative or positive result will be given to rule out melanoma or guide next steps. This test has a sensitivity of 91% and a specificity of 69%. Further, the negative predictive value (NPV) is greater than 99%.

31-GEP DecisionDx-Melanoma

The 31-GEP DecisionDx-Melanoma (Castle Biosciences) stratifies the risk positive sentinel lymph node and risk recurrence or metastasis in stage I, II or III melanoma, according to the study. It analyzes the expression of 31 genes, 28 of which are signature genes and three of which are control genes. The patient’s risk of recurrence or metastasis is categorized from lowest to highest as class 1A, class 1B/2A or class 2B. Among 1,479 patients, the test demonstrated a sensitivity of 76% and a NPV of 92% for recurrence, as well as a sensitivity of 76% and an NPV of 93% for metastasis of any stage.

8-GEP Merlin Assay

Because 85% of melanoma patients have a negative sentinel lymph node biopsy, the 8-GEP Merlin Assay (Biocartis) identifies melanoma patients who can safely forgo the biopsy. The test does this by combining GEP of eight genes and clinicopathologic variables, including Breslow thickness and patient age, to calculate the risk of lymph node metastasis. This test has an NPV of 96%.

40-GEP DecisionDx-SCC

The 40-GEP DecisionDx-SCC (Castle Biosciences) stratifies risk of metastasis into three classes: class 1, class 2A or class 2B. The test has a 40-gene signature with 34 discriminating genes and six control genes. In a cohort study of 420 patients, the 40-GEP was shown to improve the risk of metastasis stratification of cutaneous squamous cell carcinoma when combined with the clinicopathologic assessment. For tumors classified into class 2B, the test’s positive predictive value is 52.2%.

“Over the past decade, GEP has entered the skin cancer arena and serves as an adjunctive resource to help add to our understanding of tumor biology,” the authors wrote. “Due to the limitations of staging and the value of tumor biology, GEP can potentially help direct follow up and treatment decisions.”